calcimycin and ethylphenylpropiolate

We have studied the effects of the potent tumour promoter phorbol, 12-myristate, 13-acetate (PMA) and two non-promoting hyperplasiogenic compounds ethyl phenylpropriolate (EPP) and the divalent cation ionophore A23187 on the terminal differentiation of normal and transformed human keratinocytes using the loss of cloning efficiency and the formation of cornified envelopes as markers of the differentiated state. PMA induced terminal differentiation in a far greater proportion of normal keratinocytes than it did in the squamous cell carcinoma line SCC-27 but EPP and the calcium ionophores A23187 and Br-X537A had no such differential effect, possibly explaining the poor promoting ability of the last three compounds.

Topics: Alkynes; Calcimycin; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line; Cell Transformation, Neoplastic; Cells, Cultured; Clone Cells; Humans; Hyperplasia; Keratins; Phorbols; Skin; Tetradecanoylphorbol Acetate

Topics: Alkynes; Anthralin; Calcimycin; Carcinogens; Diterpenes; Epidermal Cells; Epidermis; Hyperplasia; Keratins; Phorbol Esters; Terpenes; Tetradecanoylphorbol Acetate

The percentages of dark keratinocytes was quantitatively assessed in normal epidermis of Sencar mice before and after birth and in adult epidermis after topical application of several compounds of varying promoting efficiency. The percentage of dark keratinocytes reached a maximum at the 19th day of gestation (approximately 40%) and fell abruptly after birth (approximately 3%). Old animals exhibited a very low number of dark basal cells (0.2%). After topical application of the weak promoters resiniferotoxin, anthralin, ethylphenylpropiolate, and 12-deoxyphorbol-13-2,4,6-decatrienoate, the percentage of dark cells in young adult epidermis did not differ markedly from that in control (acetone-treated) specimens. The strong first-stage promoters 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate and calcium ionophore A 23187, as well as the strong complete promoter 12-deoxyphorbol-13-deoxyphorbol-13-decanoate, induced the appearance of large numbers of dark keratinocytes, in a percentage similar to that seen after 12-O-tetradecanoylphorbol-13-acetate application (approximately 20%). The similarities between the dark keratinocytes seen after topical application of 12-O-tetradecanoylphorbol-13-acetate or other strong promoters and the dark cells observed in the fetal epidermis before the onset of the adult type of epidermal keratinization indicate that potent and/or first stage tumor promoters can be identified by their ability to induce cells resembling fetal-type dedifferentiated keratinocytes.

Topics: Administration, Topical; Age Factors; Alkynes; Animals; Anthralin; Calcimycin; Carcinogens; Epidermis; Female; Gestational Age; Hyperplasia; Methods; Mice; Phorbol Esters; Thymidine